Dhh1 promotes autophagy-related protein translation during nitrogen starvation.
Adaptor Proteins, Signal Transducing
/ genetics
Autophagy
/ physiology
Autophagy-Related Proteins
/ genetics
DEAD-box RNA Helicases
/ genetics
HEK293 Cells
Humans
Nitrogen
/ deficiency
Phosphorylation
Protein Binding
Protein Kinases
/ genetics
Protein Serine-Threonine Kinases
/ metabolism
Proto-Oncogene Proteins
/ genetics
Saccharomyces cerevisiae
/ metabolism
Saccharomyces cerevisiae Proteins
/ genetics
Transcription Factors
/ metabolism
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
30
07
2018
accepted:
22
03
2019
entrez:
12
4
2019
pubmed:
12
4
2019
medline:
7
1
2020
Statut:
epublish
Résumé
Macroautophagy (hereafter autophagy) is a well-conserved cellular process through which cytoplasmic components are delivered to the vacuole/lysosome for degradation and recycling. Studies have revealed the molecular mechanism of transcriptional regulation of autophagy-related (ATG) genes upon nutrient deprivation. However, little is known about their translational regulation. Here, we found that Dhh1, a DExD/H-box RNA helicase, is required for efficient translation of Atg1 and Atg13, two proteins essential for autophagy induction. Dhh1 directly associates with ATG1 and ATG13 mRNAs under nitrogen-starvation conditions. The structured regions shortly after the start codons of the two ATG mRNAs are necessary for their translational regulation by Dhh1. Both the RNA-binding ability and helicase activity of Dhh1 are indispensable to promote Atg1 translation and autophagy. Moreover, eukaryotic translation initiation factor 4E (EIF4E)-associated protein 1 (Eap1), a target of rapamycin (TOR)-regulated EIF4E binding protein, physically interacts with Dhh1 after nitrogen starvation and facilitates the translation of Atg1 and Atg13. These results suggest a model for how some ATG genes bypass the general translational suppression that occurs during nitrogen starvation to maintain a proper level of autophagy.
Identifiants
pubmed: 30973873
doi: 10.1371/journal.pbio.3000219
pii: PBIOLOGY-D-18-00330
pmc: PMC6459490
doi:
Substances chimiques
ATG13 protein, S cerevisiae
0
Adaptor Proteins, Signal Transducing
0
Autophagy-Related Proteins
0
Eap1 protein, S cerevisiae
0
Proto-Oncogene Proteins
0
Saccharomyces cerevisiae Proteins
0
Transcription Factors
0
Protein Kinases
EC 2.7.-
ATG1 protein, S cerevisiae
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
DDX6 protein, human
EC 3.6.1.-
DHH1 protein, S cerevisiae
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Nitrogen
N762921K75
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000219Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114131
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM053396
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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